Livers, Volume 1, Issue 1 (March 2021) – 5 articles

Laos is a landlocked country in South East Asia, ranking fifth for primary liver cancer incidence worldwide. Risk factors that might explain this worrying situation are poorly known. We conducted a review of the literature concerning the etiologies of terminal liver diseases in Laos. A double infectious burden with hepatitis B and C viruses and the liver fluke Opisthorchis viverrini seems to be the main cause of the high liver cancer incidence. Moreover, it was also suggested that mutagenic substances frequently found in tobacco, alcoholic beverages, fermented fish, and mold-contaminated cereals or nuts, which are all substances heavily consumed by Lao people, lead to the accumulation of DNA mutations in the liver cell genome causing tumor processes. However, the respective proportions of liver cancer cases attributable to each category of infections and substances consumed, as well as the histological nature of the neoplasia are still not precisely documented in Laos. The international medical and scientific communities as well as public health stakeholders should urgently consider the alarming situation of liver health in Laos to stimulate both research and subsequent implementation of prevention policies. Full article

Hepatocellular carcinoma (HCC) occurs in patients with chronic liver damage, inflammation and cirrhosis. The facilitators involved in increasing the HCC risk in the damaged liver are yet to be discovered. Diet and lifestyle have a profound effect on the liver inflammation and HCC. The term “gut liver axis” describes the bidirectional relationship between the liver and the gut, which are both anatomically and functionally related. Chronic liver damage is characterised by increased intestinal permeability that allows the translocation of various components and metabolites from the gut microbiota to the liver, resulting in liver inflammation and fibrosis. In this review, we discuss how diet-induced changes in gut microbiome composition, such as lipopolysaccharide and lipoteichoic acid, and its metabolites, such as bile acids, play a role in the pathogenesis of liver fibrosis and HCC. Full article

Background: The prevalence of metabolic liver diseases is increasing and approved pharmacological treatments are still missing. Many animal models of nonalcoholic fatty liver disease (NAFLD) show a full spectrum of fibrosis, inflammation and steatosis, which does not reflect the human situation since only up to one third of the patients develop fibrosis and nonalcoholic steatohepatitis (NASH). Methods: Seven week old C57Bl/J mice were treated with ethanol, Western diet (WD) or both. The animals’ liver phenotypes were determined through histology, immunohistochemistry, Western blotting, hepatic triglyceride content and gene expression levels. In a human cohort of 80 patients stratified by current alcohol misuse and body mass index, liver histology and gene expression analysis were performed. Results: WD diet and ethanol-treated animals showed severe steatosis, with high hepatic triglyceride content and upregulation of fatty acid synthesis. Mild fibrosis was revealed using Sirius-red stains and gene expression levels of collagen. Inflammation was detected using histology, immunohistochemistry and upregulation of proinflammatory genes. The human cohort of obese drinkers showed similar upregulation in genes related to steatosis, fibrosis and inflammation. Conclusions: We provide a novel murine model for early-stage fatty liver disease suitable for drug testing and investigation of pathophysiology. Full article

Since it was first described by the German anatomist and histologist, Joseph Hugo Vincenz Disse, the structure and functions of the space of Disse, a thin perisinusoidal area between the endothelial cells and hepatocytes filled with blood plasma, have acquired great importance in liver disease. The space of Disse is home for the hepatic stellate cells (HSCs), the major fibrogenic players in the liver. Quiescent HSCs (qHSCs) store vitamin A, and upon activation they lose their retinol reservoir and become activated. Activated HSCs (aHSCs) are responsible for secretion of extracellular matrix (ECM) into the space of Disse. This early event in hepatic injury is accompanied by loss of the pores—known as fenestrations—of the endothelial cells, triggering loss of balance between the blood flow and the hepatocyte, and underlies the link between fibrosis and organ dysfunction. If the imbalance persists, the expansion of the fibrotic scar followed by the vascularized septae leads to cirrhosis and/or end-stage hepatocellular carcinoma (HCC). Thus, researchers have been focused on finding therapeutic targets that reduce fibrosis. The space of Disse provides the perfect microenvironment for the stem cells niche in the liver and the interchange of nutrients between cells. In the present review article, we focused on the space of Disse, its components and its leading role in liver disease development. Full article